Food Sci. Technol. Res., +- (,), 23ῌ3/, ,**1

Review

Harmonization of Eastern and Western Health Knowledge; Nutrigenetics and Sasang Typology

ῌ Cherl-Ho LEE

Department of Life Science and Biotechnology, Korea University, Seoul, Korea

Received January ., ,**1; Accepted February +., ,**1

The completion of human genome project and the powerful tools of molecular biology together with bioinformatics technology give possibility to open the dialog between modern medicine and traditional remedies including Eastern medicine. Many of functional foods are originated from the traditional herbal medicine, and the scientific substantiation of the e#ectiveness of these products is required for the regulatory standards as well as for consumer protection. Needs for the reliable and e$cient methods of scientific substantiation are increasing, and nutrigenomics may provide a short-cut way to scientific evaluation of many functional food ingredients and herbal medicine which have been used in the tradition- al societies for thousand years. Studies to apply nutrigenomic methodologies to the objective classific- ation of Sasang body constitution types of Korean are reviewed. It is suggested that the empirical health food knowledge accumulated in the Eastern medicine may be explained scientifically by using the nutri- genomic methods, and it will contribute to open the custom-made nutrigenetic food age in the near future.

Keywords: Functional food, nutrigenomics, Sasang body constitution typology

Introduction are now considered as complementary and alternative Human perception on food has changed through histo- medicine (CAM) supporting the Western scientific medi- ry, from the survival food of the +3th century and before to cine. The Eastern medicine, generally known as tradi- the convenience food of the ,*th century. We all realize tional Chinese medicine (TCM), has long history of practi- that functional food and personally prescribed nutrace- cal use, although the scientific substantiations of the uticals will be the food for the ,+st century consumer of e#ectiveness are not fully established. It emphasizes the the a%uent societies (Lee, ,**0). Nutrigenomics will play organic harmony of whole body based on the Chinese old key role in prescribing the personalized health food for philosophy Yin/Yang and Five-phases theory (Maoshing, individuals. The degenerative diseases, cardiovascular +33/). Korean Eastern medicine emphasizes the type of disease, cancer, diabetes and obesity coming from im- body constitution in diagnosis and treatment of diseases, balanced nutrition mainly by overeating and reduced which is represented by Sasang body constitution typology. physical activity, became the major causes of death today Recent scientific developments make us to start to raise (Lee et al., ,**/), and people want to correct their im- the curtain between Eastern and Western health knowl- balanced nutrition by taking functional food and dietary edge. The way to nutrigenetic food age will be shorten supplements which are made for special target group. by combining the analytical approach of Western science One of the di$culties in the evaluation of the e#ective- to the holistic approach of Eastern traditional medicine. ness of a functional food or functional component is that it is true for some people but not for others. The person- Scientific Substantiation of E#ectiveness al specificity in the response to chemical components is The most important issue of functional food market often encountered in nutritional and pharmaceutical re- today is the substantiation of the e#ectiveness that pro- searches. Recent progress in human genome research and ducers claim. In the Western society, food and medicine the powerful tools of molecular biology make us enable to are strictly divided by regulation, and food can not claim explain the personal specificity by genetic basis. Al- any medicinal e#ect. In case of functional food, health though the knowledge of nutrigenetics is in the stage of benefit claims are permitted only when the su$cient impetus, it will open the age of nutrigenetic food, which scientific substantiation is provided (Ashwell, ,**,; Hasler, supplies tailor-made personal food fulfilling individual ,**,). For the scientific substantiation, we should know requirement for best fitness. the chemical composition of a food and identify the e#ec- The traditional societies in Asia as well as in Europe tive components to determine the e#ectiveness by in vitro have used natural remedies and herbal medicine, and they and in vivo, and then ultimately by human trial (Kim, ,**.). However, the present scientific approach has im- ῌ To whom correspondence should be addressed. portant drawbacks. E-mail: [email protected] Firstly, many of health and medicinal e#ects of natural 90 C. LEE products come from not a single component but the in- temporal changes in cellular small molecular weight com- tegrated action of multiple components. Not a single pounds (metabolomics e#ects) will assist in identifying component can provide absolute benefit to the body, those who respond and do not respond to dietary inter- which is made of various organs and tissues having vention. di#erent functions and chemical reactivity. This fact is Methods for the detection of SNP by scanning and recently evidenced by the nutrigenomic researches screening are now established, and the genetically regulated (Ordovas and Mooser, ,**.; Weggenmans et al., ,**+). heterogeneity in food and drug responses of individuals is The present nutritional science simplifies the matter too under investigation in many research groups. Many e$- much. Emphasizing only a known beneficial e#ect by cient high-throughput SNP genotyping technologies have concentrating the responsible component in the diet may developed, and as many as /**,*** SNPs can be detected possibly create numerous unknown adverse e#ects. The at a time (Lee, ,**0). emphasis of useful nutrients in the Western nutrition The e#ect of a dietary component on a specific pheno- science last century resulted in the consumption of highly type (e.g. plasma lipid concentration, obesity, or glycemia) refined and concentrated foods by removing fiber and can be explained by one or more genetic polymorphism filthy substances, and we all know that it is the main (Ordovas and Mooser, ,**.). The most rapid develop- cause of obesity, constipation, some cancers and heart ment of gene-diet interaction researches has been ac- diseases (Lee et al., ,**,). hieved in the area of cardiovascular disease risk, which Secondly, the response to the intake of nutrient and can be easily quantified (i.e. plasma cholesterol concentra- chemical components in food varies with people. The tion). However, the preliminary results regarding gene- statistical method to overcome this problem is apt to diet interactions in cardiovascular diseases are for the select and generalize a response which is most probable in most part inconclusive because of the limitations of cur- the cost of variable individual responses. In many cases, rent experimental design (Weggenmans et al., ,**+). In the large variation in test results makes the researcher addition, most cases of obesity, cardiovascular disease, impossible to draw any conclusion on the health e#ective- diabetes, cancer and other chronic diseases are resulted ness of a food. We should have in mind that the health by the complex interactions between several genes and benefit of a food or food component is personalized re- environmental factors (Kaput and Rodriguez, ,**.). The sponse that is hard to generalize, same as food allergy. It integrated research of various disciplines designed to is closely related to the individual genetic trait and the work on large population studies is required in order to environmental factors. relate the genotype to the resulting phenotype through systems biology. Application of Nutrigenomics Recently, the molecular biologists start to recognize Traditional Approaches that the variation in genetic make-up of individuals may The traditional societies like China and Korea have cause the variation in response to nutrient intake (Milner, long history of using food as medicine (Kim et al., +33/; ,**.). It is often observed that, with similar food con- Lee et al., +332). Traditional Chinese medicine, for exam- sumption pattern in a family, one su#ers from obesity but ple in Shennong’s Materia Medica, divides medicines into the other is normal. Food allergy and celiac disease, for three classes as follows (Lee and Kwon, ,**-). example, are another evidence of genetic variation on food +,* upper medicines, which is non-toxic used for long components (Murray, ,**/). term as food. Genetic components responsible for di#erences in die- +,* middle medicines, which have low level of toxicity tary response have been proposed for many years by the used for chronic diseases molecular biologists, and the researches to examine these +,/ lower medicines, which have high level of toxicity nutrient-gene interactions has begun recently (Ordovas used for acute illness and Mooser, ,**.; Kaput, ,**.). The individual genetic Food is considered the most important medicine to be variation is possibly explained by single nucleotide poly- used for the maintenance of health and prevention of morphism (SNP). The total number of SNP expected to illness and also at the first stage of treatment of an illness. be found in human races of the world is -ῌ+*0, which are The middle or lower class medicines are used only when less than +ῌ of human genome length (-.,ῌ+*3 bp) and the medicinal food (upper medicine) cannot cure the dis- are mostly localized in the non-coding region of human ease. The lists of medicines are found in many tradition- genome. al Chinese literatures (Dang et al., +333). They have been Many polymorphisms influence an individual’s risk of developed by thousand years of experience, mainly ac- diseases as well as the response to foods and their compo- quired by human trials, and explained the e#ectiveness nents (Kim, ,**0). Increased knowledge about the inter- on the basis of yin/yang and Five Phases theories (Lee, dependence of a response to food components on an ,**.). individual’s genetic background (nutrigenetic e#ects), the Considering food to be medicine, practitioners of tradi- cumulative e#ects of food components on genetic expres- tional medicine studied each food ingredient for its yin/ sion profiles (nutritional transcriptomics and nutritional yang property, and its applicability in diet therapy. epigenomics e#ects), the occurrence and activity of pro- Their knowledge has been compiled in numerous classical teins (nutritional proteomic e#ects), and/or the dose and medicinal books in both China and Korea for thousands Harmonization of EasternandWesternHealth Knowledge ; Nutrigenetics and Sasang Typology 91 of years, and has been practiced in everyday life at the diagram of Sasang types from a biopsycologic perspec- household level as a dietary custom (Lee et al., +33/; tive (Chae et al., ,**-). The Yang types (TaeYang and Cowmeadow, +33-; Hur, ,**,). SoYang) are extroverted and the Eum (yin) types (TaeEum Healthy food in traditional Chinese medicine implies and SoEum) are introverted. TaeYang type is very rare balancing and harmonizing yin and yang and Five Phases in Korea. The body shape of TaeEum type is larger than in a diet. A healthy diet must contain food materials that of SoEum and SoYang types. The personality trait having cold/cool (yin) and warm/hot (yang) properties and physical characteristics are symbolically expressed and five tastes evenly (Lee, +332; Kim, +33/). Therapeutic by the organ size; TaeYang - large lung and small liver, food means enforcing certain Chi (or energy) for the SoYang - large spleen and small kidney, TaeEum - large imbalanced condition (illness) of a body, and enriching liver and small lung, SoEum - large kidney and small spleen certain taste to enhance or suppress an organ function. (Lee and Choi, +330). Sasang typology emphasize the The e#ectiveness of functional food has been explained importance of individual body type in the diagnosis and systematically by this principle in the traditional Chinese treatment of diseases, and suggest prescribing di#erent medicine. medicinal treatments and food intake for di#erent body The disease susceptibility and medicine response of constitution types. individuals are also explained by the di#erences in Chi Many attempts to establish a reproducible and objec- and properties of personality trait. The body constitu- tive method of assessing Sasang constitution types have tion consideration in the Traditional Chinese Medicine is been reported after Je-Ma Lee (Song, +332;Choiet al., ,***; focused on the medicinal practice based on yin/yang and Park et al., ,***). Five Phases theories. On the other hand, Korean Sasang A questionnaire developed by KyungHee University constitution typology is based on the combination of (QSCC II) was most widely studied for the assessment of Neo-Confucianism and the medical tradition of Korea, and Sasang types, and distinctive personality traits associated describes nature as quaternary (Chae et al., ,**-). Tradi- with Sasang types could be demonstrated by using tional Chinese medicine places importance on the harmo- psychometric and anthropometric instruments (Chae et ny between humanity and nature, whereas Sasang typol- al., ,**-). Numerous food therapy schemes suggesting ogy emphasizes the harmony in social life and developing beneficial and harmful food items for di#erent Sasang one’s character. types have been reported and used by TCM doctors and dietitians in Korea (Kim et al., +33/;Leeet al., +332; Hur, Sasang Constitution Typology ,**,). Table + shows an example of Sasang food list The personal variable responses to food and medicinal beneficial for di#erent body constitution types. treatment have long been recognized in Eastern tradition- Although the assessment of constitution type of indi- al medicine and explained by the body constitution typol- viduals is not conclusive, many people in Korea follow ogy. At the end of the +3th century a Korean traditional Sasang theory in selection of their food and herbal treat- Eastern Medicine practitioner, Je-Ma Lee, proposed Sasang ment, especially when their health condition is not satis- Medicine in his book, Dongeuisusebowon (Lee and Choi, factory. A recent survey conducted in my laboratory +330). Sasang is a unique theory of categorizing people revealed that 3*ῌ of the respondents (total 2-3 Korean into four body types, TaeYang, TaeEum. SoYang, SoEum. men (//ῌ) and women (./ῌ)of,* to 0* years old) knew According to their temperaments, body shapes and other about Sasang typology and 22..ῌ believed that man general character features. Figure + shows a schematic should consume the desirable diet for his/her body type

Fig. +. A schematic diagram of Sasang types from a biopsycologic perspective (Chae et al., ,**-). 92 C. LEE

Table +. An example of Sasang food list (Kim et al., +33/).

for the prevention and cure of diseases. ././ῌ of the specific interactions on a molecular level SNP in gene people believed that they knew their own body type, regulation, translational control of RNA, enzyme regula- which were mainly determined by Eastern medicine phy- tion (proteomics) and metabolite modulation (metabolomics), sicians (,-ῌ) and by the questionnaire (+,ῌ). which occur as genotype (Ommen, ,**.). On the other Dr. Bong-Su Hur, a therapeutic food doctor in Korea, hand, in the traditional Eastern medicine numerous applies yin/yang theory in selection of food for his pa- phenotypic data on diet response to health have been tients. He believes that yin (Eum) type people should accumulated, and systematically classified by the Sasang have food of yang property, and vice versa, in order to body constitution theory. Body constitution is a genomic harmonize yin and yang in the body. Combining this trait of individuals, which is mainly determined by the principle to the Sasang constitution, he listed food items SNPs. Therefore, it is possible to relate the molecular desirable for the four body constitution types (Hur, ,**/). level genomic studies to the body constitution typology. He also suggested that celiac disease, the gluten intoler- An attempt was made to develop marker genes for the ance, is an evidence of body constitution and food rela- classification of Sasang body constitutions (Park, ,**0). tionship in Sasang theory; celiac disease occurs mainly in -. TCM school students in Korea, who were classified yin type people. identically by QSCC and by three TCM doctors, were selected and their blood samples were assayed with Nutrigenetics and Sasang Constitution Typology microarray analysis, and the Sasang-specific genes were The health e#ects of food components are related to identified. About +./ genes were di#erentially expressed Harmonization of EasternandWesternHealth Knowledge ; Nutrigenetics and Sasang Typology 93

Table ,. Genes expressed di#erentially in microarray with Sasang constitution types (Park, ,**0).

in microarray, and they were clustered into three groups, respectively, Tae-Eum, So-Yang and So-Eum. Genes ex- pressed di#erentially depending on the Sasang constitu- tion types were related to signal transduction, transport and immune response in their function (Table ,). Among them Cytochrome p./* ,D0, ,C3, +A,,SOD, genes were related to Sasang types. SOD, showed higher expres- sion in Tae-Eum type than in So-Yang and So-Eum types. Three SNPs, -.//C/A, -,/1T/C and -,.1A/G were found in /ῌ-UTR of SOD, gene. The SNP distribution pattern of So-Eum type was di#erent from those of other two types. A total of 0 haplotypes were obtained with the three SNPs. The distribution pattern of each haplotype varied Fig. ,. The relationship between nutrigenetic studies and with Sasang constitution types. Statistically SOD, ex- Sasang body constitution studies. pression was significant (Pῌ*.*/), depending on the haplotypes. However, the SNP analysis of single SOD, genes was not su$cient enough to determine the Sasang constitution types, specifically TaeYang, TaeEum, SoYang constitution type, since diverse genes were involved in and SoEum. Once they are found, we will be able to the phenotypic expression of the constitution. Although classify Sasang constitution types objectively and reli- this study is not conclusive in classification of the consti- ably, and ready to utilize the old wisdom of diet therapy tution types, it provides the possibility of using micro- which has been developed for thousand years by human array analysis and SNP analysis of specific genes for the trial, as illustrated in Fig. ,. The metabolomics studies, objective determination of the body constitution types. which depict the phenotypic consequences of genetic coding, will also assist to relate the genotypic make-up to A Novel Integrated Approach Sasang constitution types. As body constitution is a genomic trait of individuals, it Figure - illustrates the relationship between nutrigenetic will be possible to determine Sasang body constitution studies and Sasang typology, which have developed types with the molecular level genomic studies, when toward opposite directions in the East and the West. If su$cient data are accumulated. It is important to know we are able to find a channel to relate the Western analyt- the genes or SNPs responsible to the phenotypic body ical approach to the Eastern holistic approach, we will 94 C. LEE

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